Investigations in this laboratory are directed toward development of knowledge of blood platelet function in normal hemostasis, of their role in the pathogenesis of inherited and acquired bleeding disorders, and their contribution to vascular injury, atherosclerosis and thrombotic disease. Transmission and scanning electron microscopy, cytochemistry, immunocytochemistry, biochemistry, physiology, cell sizing and aggregometry are combined to facilitate the development of new information. Original concepts and technical approaches have resulted from our past work and will continue to develop from future efforts. The combination of established methods and advanced technology provide the basis for investigations into unsolved problems of platelet structural physiology and pathology. Patient problems remain of paramount interest. We have discovered two patients with the Gray Platelet Syndrome and have completed studies on their ultrastructure, cytochemistry and biochemistry demonstrating that they are deficient in a single population of alpha granules and lack the specific constituents stored in them. Work on prostaglandin synthesis and its regulation is progressing rapidly in our laboratory and includes studies on prostacyclin in vitro and in vivo. A series of links between platelet arachidonic acid activation, cyclic AMP levels and prostaglandin and non-prostaglandin dependent pathways of fatty acid ionophore generation have been established and are being explored in relationship to platelet contraction and secretion. We have recently reported the deficiency of alpha actinin in thrombasthenic platelets and are evaluating the role of this protein in platelet-platelet interaction. Studies of the platelet sarcoplasmic reticulum and the role of calmodulin in calcium activated processes in platelets are in progress. This broad-based, but carefully coordinated, approach to platelet studies will provide new and important information on platelets in health and disease.